We thank Saers and de Ru for their comments. Mechanistically, we agree with the concept that among BTX responders are those whose pathophysiologic characteristics include extracranial tissue. Traditionally, though, migraine headache was thought to originate inside rather than outside the cranium as a result of activation of sensory fibers that carry pain signals from the meninges (pia and dura) through the tentorial nerve to the spinal trigeminal nucleus in the upper cervical spinal cord. Our study challenges this notion. It raises the possibility that activation of extracranial nociceptors (sensory fibers that carry pain signals from the scalp, periosteum, and pericranial muscles) is sufficient to trigger an attack. We propose that BTX is more effective in patients who perceive their headache as imploding because such perception involves enhanced activity along extracranial rather than intracranial pain fibers. Undermining the concept that BTX reduces the frequency of migraine attacks by simply relaxing muscles that trap sensory nerves are data that show no correlation between muscle tenderness and BTX efficacy. Prophylactic treatment with BTX is not more effective in patients whose head and neck muscles are chronically tender or become tender 2 to 4 hours before the onset of an attack than in patients whose migraine attacks are not associated with any kind of muscle tenderness. The possibility that BTX may have direct inhibitory effects on unmyelinated C-nociceptors cannot be dismissed at this point. A recent article in the Journal of Comparative Neurology explains the mechanism by which extracranial pathophysiologic processes can trigger a migraine attack.1